Results: GSK744 was administered to 245 subjects across all studies. There were no drug-related SAEs. The most frequent (>5%) non-injection site reaction (ISR)-related AEs were headache (22%) and nausea (5%). Two Grade 3 AEs (creatine kinase [CK], bilirubin) and 2 Grade 4 AEs (CK, osteomyelitis) were reported as unrelated to GSK744. Treatment-emergent ≥ Grade 2 laboratory abnormalities were infrequent: total cholesterol (5%), lipase (4%), bilirubin (2%), glucose (2%) and CK (2%). 2540 post-dose ECGs were evaluated; the difference in mean change in QTcF from baseline between GSK744 and placebo groups was -2.9 msec. No relationship was observed between dose and non-ISR AE rate, ECG change from baseline and laboratory test abnormalities. ISR AEs related to GSK744 LAP injection were largely mild (93%) with no Grade 3 ISR AEs. The most frequent ISR AEs for IM and SC dosing were pain (71% and 24%), erythema (9% and 23%) and nodules (7% and 23%). Median IM ISR AE durations were ~5 days for both pain and erythema and ~22 days for nodules. There were no ISR AE-related withdrawals.

Conclusion: GSK744 as single and repeat oral doses up to 50 mg and SC/IM LAP injections up to 800 mg were well tolerated. All ISR AEs were self-limited and predominantly Grade 1. Safety analyses support continued development of both oral and parenteral GSK744 formulations.